The source for renewal of the blood
Our blood is generated in the bone marrow by so-called blood stem cells. These stem cells are able to give rise to both new stem cells (self-renewal) and to mature blood cells (differentiation). In order to maintain the production of blood, a sufficient amount of stem cells must always be present in the bone marrow.
The research team, led by professor Bo Porse recently discovered how a certain protein known as ERG plays a crucial role in securing the correct balance between self-renewal and differentiation in our bone marrow.
"By removing ERG in a biological model, we found that the blood stem cells lost their ability to create new stem cells and at the same time increased their differentiation into specialized blood cells. As a result, the blood production ceased after a very short time, since there were no stem cells left to carry out the production," says Matilda Rehn who has been in charge of the experiments.
The researchers’ experiments showed that the protein works by turning up genes that restrict the differentiation of the stem cells, and genes that increase their self-renewal. Thus, sustaining a correct level of ERG is very important since it helps to control both self-renewal and differentiation in our bone marrow.
Imbalance leads to diseaseWhen the balance between self-renewal and differentiation in the blood production is disturbed, several diseases can arise. For instance, a defect in the ability of the cells to differentiate can lead to a shortage of blood cells in bone marrow diseases like anaemia, while increased self-renewal can lead to leukaemia.
Since the ERG protein is often over expressed in certain forms of cancer including leukaemia, the researchers wished to examine if the removal of ERG could protect from leukaemia. Their experiments showed that leukaemia develops slower without ERG, but is not totally prevented from arising. This shows, that ERG plays a role in the blood production imbalance which is seen in leukaemia, but that other factors are also needed for the blood cells to develop into cancer cells.
"We believe that our results can help to explain why ERG over-expression is seen in some leukaemias. Possibly the number of blood stem cells is higher when ERG is overly active. Mutations in stem cells are especially dangerous and an increased ERG activity and thereby an elevated number of stem cells therefore increases the chance of disease," says professor Bo Porse, leader of the Porse Group.
The results are just published in the scientific journal Genes & Development and the research was supported by the Danish Cancer Society, the Lundbeck Foundation and the Novo Nordisk Foundation.
The Porse Group is part of the Finsen Laboratory and affiliated with the Biotech Research & Innovation Centre (BRIC) and the Danish Stem Cell Centre (DanStem).